Hydroxy-substituted antifungals
A compound represented by the formula I ##STR1## wherein X is independently both F or both Cl or one X is independently F and the other is independently Cl; R.sub.1 is a straight or branched chain (C.sub.3 to C.sub.8) alkyl group substituted by one or two hydroxy moieties, an ether or ester thereof (e.g., a polyether ester, heterocyclic ester amino acid ester or phosphate ester) thereof and the carbon with the asterisk (*) has the R or S absolute configuration or a pharmaceutically acceptable salt thereof and pharmaceutical compositions thereof useful for treating and/or preventing fungal infections are disclosed.
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Claims
1. A compound represented by the formula I ##STR61## wherein X is independently both F or both Cl or one X is independently F and the other is independently Cl;
- R.sub.1 is a straight or branched chain (C.sub.3 to C.sub.8) alkyl group substituted by one or two hydroxy moieties; and esters and ethers thereof
2. A compound of claim 1 wherein R.sub.1 is a straight or branched chain (C.sub.4 -C.sub.5) alkyl group substituted by at least one hydroxy moiety.
3. A compound of claim 1 wherein R.sub.1 is CHR.sub.2 R.sub.3 and which is represented by the formula II ##STR62## wherein X is independently both F or both Cl or one X is independently F and the other is independently Cl;
- R.sub.2 is H or (C.sub.1 -C.sub.3) alkyl and R.sub.3 is (C.sub.1 -C.sub.3) alkyl substituted by one hydroxy moiety and the carbons with the asterisks (*) have the R or S absolute configuration;
4. A compound of claim 1 wherein R.sub.1 is CHR.sub.2 R.sub.3 and which is represented by the formula IIa ##STR63## wherein X is independently both F or both Cl or one X is independently F and the other is independently Cl;
- R.sub.2 is H or (C.sub.1 -C.sub.3) alkyl and R.sub.3 is (C.sub.1 -C.sub.3) alkyl substituted by one hydroxy moiety and the carbon with the asterisk (*) has the R or S absolute configuration;
5. A compound of claim 3 wherein R.sub.2 or R.sub.3 is (C.sub.1 -C.sub.2)alkyl and each X is F.
6. A compound of claim 1 wherein R.sub.1 is a hydroxy-substituted C.sub.4 - or C.sub.5 -alkyl group selected from:
- --CH(C.sub.2 H.sub.5)CH(R.sub.4)CH.sub.3, --CH(C.sub.2 H.sub.5)CH.sub.2 CH.sub.2 R.sub.4, --(CH.sub.2).sub.2 --CH(R.sub.4)C.sub.2 H.sub.5, --CH(CH.sub.3)CH(R.sub.4)CH.sub.3, --CH(C.sub.2 H.sub.5)CH.sub.2 R.sub.4 and --CH(CH.sub.3)CH.sub.2 CH.sub.2 R.sub.4
- R.sub.4 is OH or an ester thereof and the carbons with the asterisk(*) have the R or S absolute configuration or a pharmaceutically acceptable salt thereof.
7. A compound represented by formula III ##STR64## wherein R.sub.5 is ##STR65## or an ester thereof or a pharmaceutically acceptable salt thereof.
8. A compound represented by the formula IV ##STR66## wherein R.sub.9 =--CH(C.sub.2 H.sub.5)CH(R.sub.6)CH.sub.3 or --CH(CH.sub.3)CH(R.sub.6)CH.sub.3
- R.sub.6 =is OH, and the carbons with the asterisks (*) have the R or S absolute configuration; or an ester or ether thereof or a pharmaceutically acceptable salt thereof.
9. A compound represented by the formula IVa ##STR67## wherein R.sub.9 =--CH(C.sub.2 H.sub.5)CH(R.sub.6)CH.sub.3 or --CH(CH.sub.3)CH(R.sub.6)CH.sub.3
- R.sub.6 is OH, and the carbon with the asterisk (*) has the R or S absolute configuration; or an ester thereof or a pharmaceutically acceptable salt thereof.
10. A pharmaceutical composition for treating or preventing fungal infection comprising an antifungally effective amount of a compound of claim 1 together with a pharmaceutically acceptable carrier therefor.
11. A method of treating and/or preventing fungal infections in a mammal afflicted with same which comprises administering an antifungally effective amount of a compound of claim 1 sufficient for such treating or preventing.
12. The pharmaceutical composition of claim 10 wherein the mode of administration is oral or parenteral.
13. The compound of claim 1 wherein the ester is a polyether ester.
14. The compound of claim 7 wherein the ester is a polyether ester.
15. The compound of claim 1 wherein the ester is an amino acid ester.
16. The compound of claim 7 wherein the ester is an amino acid ester.
17. The compound of claim 7 wherein the amino acid ester is derived from reaction of glycine and a compound of formula III.
18. The compound of claim 1 wherein the ester is a phosphate ester.
19. The compound of claim 7 wherein the ester is a phosphate ester.
Type: Grant
Filed: Jun 17, 1996
Date of Patent: Dec 16, 1997
Assignee: Schering Corporation (Kenilworth, NJ)
Inventors: Anil K. Saksena (Upper Montclair, NJ), Viyyoor M. Girijavallabhan (Parsippany, NJ), Raymond G. Lovey (West Caldwell, NJ), Russell E. Pike (Stanhope, NJ)
Primary Examiner: Matthew V. Grumbling
Assistant Examiner: Brenda Coleman
Attorney: Thomas D. Hoffman
Application Number: 8/664,758
International Classification: A61K 31495; C07D40300;